Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patie...

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Published in:	Frontiers in immunology Vol. 13; p. 917232
Main Authors:	Baßler, Kevin, Fujii, Wataru, Kapellos, Theodore S, Dudkin, Erika, Reusch, Nico, Horne, Ari, Reiz, Benedikt, Luecken, Malte D, Osei-Sarpong, Collins, Warnat-Herresthal, Stefanie, Bonaguro, Lorenzo, Schulte-Schrepping, Jonas, Wagner, Allon, Günther, Patrick, Pizarro, Carmen, Schreiber, Tina, Knoll, Rainer, Holsten, Lisa, Kröger, Charlotte, De Domenico, Elena, Becker, Matthias, Händler, Kristian, Wohnhaas, Christian T, Baumgartner, Florian, Köhler, Meike, Theis, Heidi, Kraut, Michael, Wadsworth, 2nd, Marc H, Hughes, Travis K, Ferreira, Humberto J, Hinkley, Emily, Kaltheuner, Ines H, Geyer, Matthias, Thiele, Christoph, Shalek, Alex K, Feißt, Andreas, Thomas, Daniel, Dickten, Henning, Beyer, Marc, Baum, Patrick, Yosef, Nir, Aschenbrenner, Anna C, Ulas, Thomas, Hasenauer, Jan, Theis, Fabian J, Skowasch, Dirk, Schultze, Joachim L
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 28-07-2022
Subjects:	blood bronchoalveolar lavage Chemotaxis - physiology chronic obstructive pulmonary disease Humans Immunology impaired immune activation macrophage Macrophages - metabolism Macrophages, Alveolar monocyte Monocytes - metabolism Pulmonary Disease, Chronic Obstructive TGF-β1 macrophage monocyte blood bronchoalveolar lavage impaired immune activation chronic obstructive pulmonary disease
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Summary:	Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors share last authorship These authors share first authorship This article was submitted to Systems Immunology, a section of the journal Frontiers in Immunology Reviewed by: Subhash Kumar Tripathi, University of Turku, Finland; Roland Lang, University Hospital Erlangen, Germany Edited by: Alexander Hoffmann, University of California, Los Angeles, United States Present Address: Kevin Baßler, Aimed analytics, Bonn, Germany; Wataru Fujii, Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2022.917232